Keratin-8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment.
Keratin 8 (K8) is the major intermediate filament protein present in intestinal epithelia. Depending on the mouse genetic background, absence of K8 causes embryonic lethality or colonic hyperplasia and colitis. We studied disease progression, the inflammatory responses, and role of luminal bacteria in K8-null mice in order to characterize the intestinal pathology of K8-associated colitis. Colon lymphocytes were isolated for analysis of their phenotype and cytokine production, and vascular and lymphocyte adhesion molecule expression in K8-/- mice of varying ages. K8-/- mice had a marked increase in TCR(beta)-positive/CD4-positive T cells infiltrating the colon lamina propria, in association with enhanced Th2 cytokine (IL-4, IL-5 and IL-13) production. K8-/- mice show early signs of inflammation even prior to weaning, that increases with age, and their epithelial cells overexpress MHC class II antigens. The chronic colitis is related to increased CD4-positive infiltrating T cells displaying memory and naive phenotypes, and an altered vascular endothelium with aberrant expression of peripheral node addressin. Analysis of normal gut-specific homing molecules, reveals an increased number of alpha(4)beta(7)-positive cells and vascular mucosal addressin cell adhesion molecule-1 in K8-null colons. Antibiotic treatment markedly decreased colon inflammation and ion transporter AE1/2 mistargeting, indicating that luminal bacteria play an important role in the observed phenotype. Therefore, K8-null mice develop chronic spontaneous Th2-type colitis due to a primary epithelial rather than immune cell defect, which is amenable to antibiotic therapy. These mice provide a model to investigate epithelial-leukocyte and epithelial-microbial cross-talk.


[Common infections of the ear, nose, and throat].
Infectious diseases of the ear, nose and throat are common reasons why patients visit their family physician. Therefore, the aim of this mini-review is to give an overview of the most important and frequent infectious diseases of the ear, nose and throat, the appropriate diagnostic measurements and therapy with relevance for the family physician. Most of these infectious diseases can be treated by the family physician and do not necessarily need to be seen by an ENT-specialist.


Exploration of an innovative draw solution for a forward osmosis-membrane distillation desalination process.
Forward osmosis (FO) has emerged as a viable technology to alleviate the global water crisis. The greatest challenge facing the application of FO technology is the lack of an ideal draw solution with high water flux and low reverse salt flux. Hence, the objective of this study was to enhance FO by lowering reverse salt flux and maintaining high water flux; the method involved adding small concentrations of Al2(SO4)3 to a MgCl2 draw solution. Results showed that 0.5 M MgCl2 mixed with 0.05 M of Al2(SO4)3 at pH 6.5 achieved a lower reverse salt flux (0.53 gMH) than that of pure MgCl2 (1.55 gMH) using an FO cellulose triacetate nonwoven (CTA-NW) membrane. This was due possibly to the flocculation of aluminum hydroxide in the mixed draw solution that constricted membrane pores, resulting in reduced salt diffusion. Moreover, average water fluxes of 4.09 and 1.74 L/m2-h (LMH) were achieved over 180 min, respectively, when brackish water (5 g/L) and sea water (35 g/L) were used as feed solutions. Furthermore, three types of membrane distillation (MD) membranes were selected for draw solution recovery; of these, a polytetrafluoroethylene membrane with a pore size of 0.45 μm proved to be the most effective in achieving a high salt rejection (99.90%) and high water flux (5.41 LMH) in a diluted draw solution.


Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses.
Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.


Novel method for analysis of allele specific expression in triploid Oryzias latipes reveals consistent pattern of allele exclusion.
Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18%) displayed a wide range of ASE levels. Interestingly the majority of genes (78%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.


Self-controlled feedback is effective if it is based on the learner's performance: a replication and extension of Chiviacowsky and Wulf (2005).
The learning advantages of self-controlled feedback schedules compared to yoked schedules have been attributed to motivational influences and/or information processing activities with many researchers adopting the motivational perspective in recent years. Chiviacowsky and Wulf (2005) found that feedback decisions made before (Self-Before) or after a trial (Self-After) resulted in similar retention performance, but superior transfer performance resulted when the decision to receive feedback occurred after a trial. They suggested that the superior skill transfer of the Self-After group likely emerged from information processing activities such as error estimation. However, the lack of yoked groups and a measure of error estimation in their experimental design prevents conclusions being made regarding the underlying mechanisms of why self-controlled feedback schedules optimize learning. Here, we revisited Chiviacowsky and Wulf's (2005) design to investigate the learning benefits of self-controlled feedback schedules. We replicated their Self-Before and Self-After groups, but added a Self-Both group that was able to request feedback before a trial, but could then change or stay with their original choice after the trial. Importantly, yoked groups were included for the three self-controlled groups to address the previously stated methodological limitation and error estimations were included to examine whether self-controlling feedback facilitates a more accurate error detection and correction mechanism. The Self-After and Self-Before groups demonstrated similar accuracy in physical performance and error estimation scores in retention and transfer, and both groups were significantly more accurate than the Self-Before group and their respective Yoked groups (p's < 0.05). Further, the Self-Before group was not significantly different from their yoked counterparts (p's > 0.05). We suggest these findings further indicate that informational factors associated with the processing of feedback for the development of one's error detection and correction mechanism, rather than motivational processes are more critical for why self-controlled feedback schedules optimize motor learning.


Response of the nose to exercise in healthy subjects and in patients with rhinitis and asthma.
Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls. Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test. Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise. These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.


School Violence, Depressive Symptoms, and Help-seeking Behavior: A Gender-stratified Analysis of Biethnic Adolescents in South Korea.
In South Korea (hereafter Korea), the number of adolescent offspring of immigrants has rapidly increased since the early 1990s, mainly due to international marriage. This research sought to examine the association between the experience of school violence and mental health outcomes, and the role of help-seeking behaviors in the association, among biethnic adolescents in Korea. We analyzed cross-sectional data of 3627 biethnic adolescents in Korea from the 2012 National Survey of Multicultural Families. Based on the victim's help-seeking behavior, adolescents who experienced school violence were classified into three groups: 'seeking help' group; 'feeling nothing' group; 'not seeking help' group. Multivariate logistic regression was applied to examine the associations between the experience of school violence and depressive symptoms for males and females separately. In the gender-stratified analysis, school violence was associated with depressive symptoms in the 'not seeking help' (odds ratio [OR], 7.05; 95% confidence interval [CI], 3.76 to 13.23) and the 'seeking help' group (OR, 2.77; 95% CI, 1.73 to 4.44) among male adolescents after adjusting for potential confounders, including the nationality of the immigrant parent and Korean language fluency. Similar associations were observed in the female groups. However, in the 'feeling nothing' group, the association was only significant for males (OR, 8.34; 95% CI, 2.82 to 24.69), but not females (OR, 0.77; 95% CI, 0.18 to 3.28). This study suggests that experience of school violence is associated with depressive symptoms and that the role of victims' help-seeking behaviors in the association may differ by gender among biethnic adolescents in Korea.


Tensor species and symmetric functions.
An equivariant representation of the symmetric group Sn (equivariant representation from here on) is defined as a particular type of tensor species. For any tensor species R the characteristic generating function of R is defined in a way that generalizes the Frobenius characters of representations of the symmetric groups. If R is an equivariant representation, then the characteristic is a homogeneous symmetric function. The combinatorial operations on equivariant representations correspond to formal operations on the respective characteristic functions. In particular, substitution of equivariant representations corresponds to plethysm of symmetric functions. Equivariant representations are constructed that have as characteristic the elementary, complete, and Schur functions. Bijective proofs are given for the formulas that connect them with the monomial symmetric functions.


Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).
Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.


Factors affecting satisfaction on antenatal care services in Sarawak, Malaysia: evidence from a cross sectional study.
High levels of satisfaction among women with the antenatal care services will increase the compliance of antenatal visits during pregnancy. Thus, this study was done to assess the level of satisfaction among women on the quality of antenatal care received and the factors influencing thereof. This was a cross-sectional study conducted in the three zones of Sarawak. Women aged 18 years and above, irrespective of ethnic groups, having children aged 3 years and below were included in the study. Data was collected by face-to-face interview using interview schedule. A validated Patient Satisfaction Questionnaire (PSQ-18) was used to assess the satisfaction with antenatal care. A total of 1236 data was analysed using IBM SPSS version 22.0. A p value <0.05 was considered as statistically significant. A multinomial logistic regression analysis revealed that Bidayuh 17.4 % was less likely to be highly satisfied with antenatal care. Similarly, respondents with secondary level of education 29.9 % were less likely to be highly satisfied, whereas, respondents having primary level of education, 1.6 % were less likely to be highly satisfied. However, those who did not spend any money as out of pocket expenses were 1.935 times more likely to be highly satisfied with antenatal care. Overall the studied women were satisfied with the antenatal care services. Ethnicity, level of education and out of pocket expenses appeared to be important predictors of satisfaction with antenatal care. The finding recommends the community-based and language-specific interventions should be implemented to sustain the satisfaction of maternal care.


Health Education for Musicians.
Context and aims: Many musicians suffer for their art, and health is often compromised during training. The Health Promotion in Schools of Music (HPSM) project has recommended that health education should be included in core curricula, although few such courses have been evaluated to date. The aim of the study was to design, implement and evaluate a compulsory health education course at a UK conservatoire of music. Methods: The course design was informed by a critical appraisal of the literature on musicians' health problems and their management, existing health education courses for musicians, and the HPSM recommendations. It was delivered by a team of appropriately-qualified tutors over 5 months to 104 first-year undergraduate students, and evaluated by means of questionnaires at the beginning and end of the course. Thirty-three students who had been in their first year the year before the course was introduced served as a control group, completing the questionnaire on one occasion only. Items concerned: hearing and use of hearing protection; primary outcomes including perceived knowledge and importance of the topics taught on the course; and secondary outcomes including physical and psychological health and health-promoting behaviors. The content of the essays written by the first-year students as part of their course assessment served as a guide to the topics they found most interesting and relevant. Results: Comparatively few respondents reported using hearing protection when practicing alone, although there was some evidence of hearing loss, tinnitus, and hyperacusis. Perceived knowledge of the topics on the course, and awareness of the risks to health associated with performing music, increased, as did self-efficacy; otherwise, there were negative effects on secondary outcomes, and few differences between the intervention and control groups. The topics most frequently covered in students' essays were managing music performance anxiety, and life skills and behavior change techniques. Conclusion: There is considerable scope for improving music students' physical and psychological health and health-related behaviors through health education, and persuading senior managers, educators and students themselves that health education can contribute to performance enhancement.


Stochastic hydro-economic model for groundwater quality management using Bayesian networks.
A strong normative development in Europe, including the Nitrate Directive (1991) and the Water Framework Directive (WFD) (2000), has been promulgated. The WFD states that all water bodies have to reach a good quantitative and chemical status by 2015. It is necessary to consider different objectives, often in conflict, for tackling a suitable assessment of the impacts generated by water policies aimed to reduce nitrate pollution in groundwater. For that, an annual lumped probabilistic model based on Bayesian networks (BNs) has been designed for hydro-economic modelling of groundwater quality control under uncertain conditions. The information introduced in the BN model comes from different sources such as previous groundwater flow and mass transport simulations, hydro-economic models, stakeholders and expert opinion, etc. The methodology was applied to the El Salobral-Los Llanos aquifer unit within the 'Easter Mancha' groundwater body, which is one of the largest aquifers in Spain (7,400 km(2)), included in the Júcar River Basin. Over the past 30 years, socioeconomic development within the region has been mainly depending on intensive use of groundwater resources for irrigating crops. This has provoked a continuous groundwater level fall in the last two decades and significant streamflow depletion in the connected Júcar River. This BN model has proved to be a robust Decision Support System for helping water managers in the decision making process.


The origins of Minnesota's mid-level dental practitioner: alignment of problem, political and policy streams.
Using John Kingdon's agenda-setting model, this paper explores how Minnesota came to legislate a mid-level dental practitioner to its oral health workforce. Using a pluralist framework embracing the existence of various interests and convictions, this analysis highlights the roles of issue formation, agenda setting and politics in policymaking. Using Kingdon's agenda-setting model as a theoretical lens, and applying case study methodology, this paper analyzes how Minnesota came to legislate a mid-level dental practitione to its oral health workforce. Data have come from scholarly research, governmental and foundation agency reports, interviews with leaders involved in the mid-level dental practitioner initiative, news articles, and Minnesota statute. After 2 years of contentious and challenging legislative initiatives, the problem, policy and political streams converged and aligned with the compromise passage of a bill legalizing mid-level dental practitioner practice. The Minnesota Dental Therapist Law was the first-in-the-nation licensing law to develop a new dental professional workforce model to address access to oral health care. The Minnesota mid-level dental practitioner initiative demonstrates the important convergence and alignment of the access to oral health care problem and the subsequent collaboration between political interest groups and policymakers. Through partnerships and pluralist compromise, mid-level dental practitioner champions were able to open the policy window to move this legislation to law, enhancing the oral health workforce in Minnesota.


Vessel-encoded dynamic magnetic resonance angiography using arterial spin labeling.
A new noninvasive MRI method for vessel-selective angiography is presented. The technique combines vessel-encoded pseudocontinuous arterial spin labeling with a two-dimensional dynamic angiographic readout and was used to image the cerebral arteries in healthy volunteers. Time-of-flight angiograms were also acquired prior to vessel-selective dynamic angiography acquisitions in axial, coronal, and/or sagittal planes, using a 3-T MRI scanner. The latter consisted of a vessel-encoded pseudocontinuous arterial spin labeling pulse train of 300 or 1000 ms followed by a two-dimensional thick-slab flow-compensated fast low-angle shot readout combined with a segmented Look-Locker sampling strategy (temporal resolution = 55 ms). Selective labeling was performed at the level of the neck to generate individual angiograms for both right and left internal carotid and vertebral arteries. Individual vessel angiograms were reconstructed using a bayesian inference method. The vessel-selective dynamic angiograms obtained were consistent with the time-of-flight images, and the longer of the two vessel-encoded pseudocontinuous arterial spin labeling pulse train durations tested (1000 ms) was found to give better distal vessel visibility. This technique provides highly selective angiograms quickly and noninvasively that could potentially be used in place of intra-arterial x-ray angiography for larger vessels.


Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.
Alcoholism is a complex disease with both genetic and environmental risk factors. To identify genes that affect the risk for alcoholism, we systematically ascertained and carefully assessed individuals in families with multiple alcoholics. Linkage and association analyses suggested that a region of chromosome 4p contained genes affecting a quantitative endophenotype, brain oscillations in the beta frequency range (13-28 Hz), and the risk for alcoholism. To identify the individual genes that affect these phenotypes, we performed linkage disequilibrium analyses of 69 single-nucleotide polymorphism (SNPs) within a cluster of four GABA(A) receptor genes, GABRG1, GABRA2, GABRA4, and GABRB1, at the center of the linked region. GABA(A) receptors mediate important effects of alcohol and also modulate beta frequencies. Thirty-one SNPs in GABRA2, but only 1 of the 20 SNPs in the flanking genes, showed significant association with alcoholism. Twenty-five of the GABRA2 SNPs, but only one of the SNPs in the flanking genes, were associated with the brain oscillations in the beta frequency. The region of strongest association with alcohol dependence extended from intron 3 past the 3' end of GABRA2; all 43 of the consecutive three-SNP haplotypes in this region of GABRA2 were highly significant. A three-SNP haplotype was associated with alcoholism, with P=.000000022. No coding differences were found between the high-risk and low-risk haplotypes, suggesting that the effect is mediated through gene regulation. The very strong association of GABRA2 with both alcohol dependence and the beta frequency of the electroencephalogram, combined with biological evidence for a role of this gene in both phenotypes, suggest that GABRA2 might influence susceptibility to alcohol dependence by modulating the level of neural excitation.


Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation.
Tendon stem cells (TSCs) exhibit a high self-renewal capacity, multi-differentiation potential, and low immunogenicity; thus, these cells might provide a new cell source for tendon repair and regeneration. TSCs are exposed to increased oxidative stress at tendon injury sites; however, how TSCs maintain their stemness under oxidative stress is not clear. In this study, we found that H2O2 treatment increased ROS accumulation in human TSCs (hTSCs) and resulted in loss of self-renewal capacity and stemness, as reflected in reduced colony formation and proliferation, decreased expression of the stemness markers Nanog, Oct-4, NS, and SSEA-4, and impaired differentiation capability. These H2O2-induced damages were prevented by pretreatment with starvation or rapamycin. Pretreatment with starvation or rapamycin prior to H2O2 exposure also led to decreased intracellular and mitochondrial ROS accumulation along with increased autophagic activity, as manifested in increased LC3 cleavage, Beclin-1 expression, and GFP-LC3-labeled autophagosome formation. Autophagy inhibition by 3-MA or CQ, or by shRNA silencing of Agt-7 or Beclin-1 reduced the protective effects of starvation and rapamycin on H2O2-treated hTSCs. Thus, the findings of this study suggest that autophagy prevents oxidative stress-induced loss of self-renewal capacity and stemness in hTSCs through suppression of ROS accumulation.


The Role of Alpha-Band Brain Oscillations as a Sensory Suppression Mechanism during Selective Attention.
Evidence has amassed from both animal intracranial recordings and human electrophysiology that neural oscillatory mechanisms play a critical role in a number of cognitive functions such as learning, memory, feature binding and sensory gating. The wide availability of high-density electrical and magnetic recordings (64-256 channels) over the past two decades has allowed for renewed efforts in the characterization and localization of these rhythms. A variety of cognitive effects that are associated with specific brain oscillations have been reported, which range in spectral, temporal, and spatial characteristics depending on the context. Our laboratory has focused on investigating the role of alpha-band oscillatory activity (8-14 Hz) as a potential attentional suppression mechanism, and this particular oscillatory attention mechanism will be the focus of the current review. We discuss findings in the context of intersensory selective attention as well as intrasensory spatial and feature-based attention in the visual, auditory, and tactile domains. The weight of evidence suggests that alpha-band oscillations can be actively invoked within cortical regions across multiple sensory systems, particularly when these regions are involved in processing irrelevant or distracting information. That is, a central role for alpha seems to be as an attentional suppression mechanism when objects or features need to be specifically ignored or selected against.


Optimisation of sampling for the temporal monitoring of technetium-99 in the Arctic marine environment.
Monitoring of the marine environment for radioactivity, for both radiological protection and oceanographic purposes, remains an expensive and labour intensive activity due to the large sample volumes needed and the complex and lengthy analytical procedures required to measure low levels of contamination. Because of this, some consideration must be given to the design of sampling plans to ensure effective and efficient sampling that can be defended on the basis of scientific rationale. This article tests the hypothesis that geostatistical techniques may prove of use in the optimisation and design of sampling regimes for the monitoring of temporal fluctuations in the levels of technetium at a location in the Norwegian Arctic marine environment. The level of temporal correlation exhibited by two relevant time series was investigated and the information used to observe the effect of sampling frequency on the production of monthly estimates of activity of technetium in both seawater and seaweed. The results indicate that reduced sampling frequency allows production of estimates that acceptably replicate the actual data and that use of geostatistical procedures may offer advantages in the planning of monitoring systems for marine radioactivity. The use of an oceanographic model was also investigated as a means of assessing the temporal correlation prior to actual sampling, an approach that may offer significant advantages by reducing the need to have lengthy time series prior to designing sampling regimes.


Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cells.
Human intravenous immunoglobulins (IVIG) are widely used as immunomodulators because of their ability to modify the course of various immune-mediated diseases. We investigated the mechanisms responsible for the regulatory effects of IVIG on in vitro human peripheral blood mononuclear cell (PBMC) cytokine production. Pre-incubation of PBMCs with IVIG inhibited lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulated cytokine secretion. Pre-incubation of PBMCs with IVIG induced a significant inhibition of LPS-stimulated (IL-6) secretion (p = 0.045); the effect on tumor necrosis factor-alpha (TNF-alpha) secretion was not significant (p = 0.234). Pre-incubation of PBMCs with IVIG inhibited IL-6 secretion (p = 0.033) stimulated with anti-CD14 antibody cross-linking but had no significant effect on TNF-alpha secretion (p = 0.125). PBMC pre-incubation with anti-CD14-blocking antibody induced a significant reduction (p = 0.042) in LPS-stimulated TNF-alpha secretion in comparison with a non-significant reduction (p =0.256) noted with IVIG pre-treatment. In contrast, pre-incubation of PBMCs with anti-CD14 antibody did not induce a significant reduction in LPS-stimulated IL-6 secretion (p = 0.166) in comparison with a significant reduction (p = 0.001) induced with IVIG pre-treatment. Our data suggest that the immunoregulatory properties of IVIG may rely on several mechanisms, some of which may be independent of CD14. Our data also showed that cross-linking cell membrane-bound IVIG with anti-human kappa- and lambda-chain antibodies resulted in cytokine secretion levels similar to those elicited by LPS. In addition, intracellular DNA staining results did not support the involvement of apoptosis in the regulatory mechanisms of IVIG. This data may further our understanding of the immunoregulatory effects exerted by IVIG on the production of inflammatory-response mediators.


Taxonomic notes: a proposal for recording the properties of putative taxa of procaryotes.
The problem that the proposal for recording the properties of putative taxa of procaryotes attempts to redress arises because the International Code of Nomenclature of Bacteria is not able to provide sensible regulation of nomenclature for new taxa defined by very limited data, such as a nucleotide sequence for a small portion of the genome. The constructors of the original code (1957) and the Judicial Commission considering the 1976 and 1990 revisions did not foresee or act upon the possibilities for molecular description and typification of procaryotes that were not yet cultivable. As a result, formal names are being proposed for uncultivated procaryotes whose uniqueness is defined only by very limited characteristics, such as differences in a molecular sequence. As the editors of two journals concerned with the systematics of procaryotes, we recognize that the problem will increase as the available technology gains wider use and becomes easier to apply. Accordingly, this note is presented in advance of discussions by the International Committee on Systematic Bacteriology at the forthcoming congress (July 1994) so that there may be discussions and reaction by colleagues.


Functional role for heat shock factors in the transcriptional regulation of human RANK ligand gene expression in stromal/osteoblast cells.
RANK Ligand (RANKL) is a critical osteoclastogenic factor that is expressed on stromal cells and osteoblasts. Most resorption stimuli induce osteoclast formation by modulating RANKL gene expression in marrow stromal/osteoblast cells. However, it is unclear how these stimuli modulate RANKL gene expression in the bone microenvironment. To characterize the transcriptional control of human RANKL gene expression in stromal/osteoblast cells, we PCR-amplified and cloned a 2-kb 5'-flanking sequence of the RANKL gene, using normal human osteoblast derived genomic DNA as a template. Sequence analysis identified the presence of several potential Heat Shock Factor (HSF) responsive elements (HSE) in the human RANKL gene promoter region. Co-expression of HSF-1 or HSF-2 with the RANKL gene promoter-luciferase reporter plasmid in human osteoblastic cells (NOBC) demonstrated a 2-fold and 4.5-fold increase in promoter activity, respectively. RT-PCR analysis for HSF-1 and 2 mRNA expression in human bone marrow-derived stromal cells (SAKA-T) and osteoblast cells detected only HSF-2 expression. As evident from EMSA analysis, in contrast to 1,25(OH)(2)D(3) SAKA-T cells treated with b-FGF demonstrated increased levels of HSF-2 binding to the HSE present in the RANKL gene promoter region. Immunocytochemical staining further confirmed nuclear localization of HSF-2 in both SAKA-T transformed stromal cells and human bone marrow derived primary stromal/preosteoblastic cells in response to b-FGF treatment. Furthermore, b-FGF treatment of SAKA-T cells transfected with the luciferase reporter plasmid containing the hRANKL HSE region (-2 kb to -1275 bp) upstream to a heterologous promoter showed increased levels of transactivation. Western blot analysis further demonstrated enhanced levels of RANKL expression and HSP-27 phosphorylation in SAKA-T cells treated with b-FGF. In addition, overexpression of HSF-2 in SAKA-T cells resulted in a 5-fold increase in the levels of RANKL expression in these cells. These data further suggest that HSF-2 is a downstream target of b-FGF to induce RANKL expression in stromal/osteoblast cells, and that HSF may play an important role in modulating RANKL gene expression in the bone microenvironment.


Body fat distribution in relation to physical activity and smoking habits in 38-year-old European men. The European Fat Distribution Study.
The authors studied 512 European men all born in 1950 from six different towns in the period October 1988 to May 1989. Anthropometric measurements were taken, including weight, height, and circumferences (waist, hip, thigh). Educational level, activity scores and information on smoking habits were obtained from a questionnaire. Higher educational level was associated with lower body mass index, waist/hip ratio, and waist/thigh ratio. The sports activity score was negatively related to waist/hip ratio (beta +/- standard error of the mean (SEM): -0.009 +/- 0.003) and waist/thigh ratio (-0.041 +/- 0.007), and this could be attributed to a negative relation with waist circumference and a positive relation to thigh circumference. Smoking habits were not related to body mass index but heavy smokers had larger waist circumferences (difference +/- SEM: 1.4 +/- 0.5 cm) as well as higher waist/hip ratios (difference +/- SEM: 0.014 +/- 0.005) and waist/thigh ratios (0.043 +/- 0.013) compared with men who never smoked. These associations between activity scores and smoking habits and fat distribution remained after adjustment for each other and for body mass index and educational level. The authors conclude that physical activity and smoking are independently related to indicators of fat distribution and may be potential confounders in the relations between fat distribution, risk factors, and disease.


Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.


[Recurrence and treatment of primary liver cancer after radical hepatectomy].
From Jan. 1961 to Dec. 1988, 188 patients with hepatocellular carcinoma had radical resection. AFP concentration of all patients turned negative after the operation or was originally negative. By the end of August 1989, 85 patients had cancer recurrence after surgery with a median of 18 months (1-106 months). Recurrence happened mostly in the first and second year postoperation. The cumulative recurrence was 35.8% in one year, 62.4% in two years, and 95.3% in 5 years. Serial measurement of serum AFP and ultrasonography were found useful for early detection of cancer recurrence. For the patients with cancer recurrence, reoperation was the treatment of choice, and 49.4% of them underwent the second resection, with normal AFP concentrations in 58.6% of the patients after surgery. The 1-, 3-, and 5-year survival rates were 50%, 27.3%, and 23.5% after the second resection, respectively. Chemotherapy combined with immunotherapy was effective to prolong the recurrence-free survival time after the primary resection.


Polygenic risk score for ACE-inhibitor-associated cough based on the discovery of new genetic loci.
To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs). A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker. Controls were defined as persons who continued ACEi treatment for at least 1 year. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed for ACEi discontinuation risk by mixed model regression analysis. Summary statistics from the individual cohorts were meta-analyzed with a fixed-effects model. To test for association with specific ACEi-associated ADRs, any genome-wide significant (P < 5 × 10-8) ACEi discontinuation variants was tested for association with ACEi-associated cough and angioedema. A polygenetic risk score (PRS) based on ACEi discontinuation GWAS data was constructed and tested for association with ACEi-associated cough and angioedema in two population-based samples. In total, seven genetic genome-wide loci were identified, of which six were previously unreported. The strongest association with ACEi discontinuation was at 20q13.3 (NTSR1; OR: 1.21; 95% CI: 1.17-1.24; P = 2.1 × 10-34). Five of seven lead variants were associated with ACEi-associated cough, whereas none were associated with ACEi-associated angioedema. The ACEi discontinuation PRS was associated with ACEi-associated cough in a dose-response manner but not with ACEi-associated angioedema. ACEi discontinuation was genetically correlated with important causes for cough, including gastro-esophageal reflux disease, allergic rhinitis, hay fever, and asthma, which indicates partly shared genetic underpinning between these traits. This study showed the advantage of using prescription patterns to discover genetic links with ADRs. In total, seven genetic loci that associated with ACEi discontinuation were identified. There was evidence of a strong association between our ADR phenotype and ACEi-associated cough. Taken together, these findings increase insight into the pathophysiological processes that underlie ACEi-associated ADRs.


Assessment of plaque evolution in coronary bifurcations located beyond everolimus eluting scaffolds: serial intravascular ultrasound virtual histology study.
To evaluate the atherosclerotic evolution in coronary bifurcations located proximally and distally to a bioresorbable scaffold. Thirty bifurcations located >5 mm beyond the scaffolded segment, being investigated with serial intravascular ultrasound virtual histology (IVUS-VH) examinations, at baseline and 2-years, in patients enrolled in the ABSORB cohort B1 study were included in this analysis. In each bifurcation, the frames portraying the proximal rim, in-bifurcation, and distal rim of the ostium of the side branch were analyzed. The geometric parameters and plaque types were evaluated at baseline and 2-years follow-up. There were no significant differences in the geometrical parameters such as lumen, vessel and plaque areas as well as in the composition of the atheroma between baseline and 2-years follow-up.When we separately examined the bifurcations located proximally and distally to the scaffolded segment, no changes were found at the distal bifurcations, while at the proximal bifurcations there was a statistical significant decrease in the plaque burden (36.67 ± 13.33% at baseline vs. 35.06 ± 13.20% at 2 years follow-up, p = 0.04).Ten necrotic core rich plaques were found at baseline, of which 2 regressed to either fibrotic plaque or to intimal thickening at 2 years follow-up. The other 8 did not change. Disease progression was noted in 3 plaques (1 adaptive intimal thickening, 1 fibrotic and 1 fibrocalcific plaque) that evolved to necrotic rich plaques. Plaque regression was noted at the bifurcations located proximally to the bioresorbable scaffold but not at these located distally. Additional studies are required to confirm this finding and examine further the effect of drug elution on atherosclerotic evolution.


RES complex is associated with intron definition and required for zebrafish early embryogenesis.
Pre-mRNA splicing is a critical step of gene expression in eukaryotes. Transcriptome-wide splicing patterns are complex and primarily regulated by a diverse set of recognition elements and associated RNA-binding proteins. The retention and splicing (RES) complex is formed by three different proteins (Bud13p, Pml1p and Snu17p) and is involved in splicing in yeast. However, the importance of the RES complex for vertebrate splicing, the intronic features associated with its activity, and its role in development are unknown. In this study, we have generated loss-of-function mutants for the three components of the RES complex in zebrafish and showed that they are required during early development. The mutants showed a marked neural phenotype with increased cell death in the brain and a decrease in differentiated neurons. Transcriptomic analysis of bud13, snip1 (pml1) and rbmx2 (snu17) mutants revealed a global defect in intron splicing, with strong mis-splicing of a subset of introns. We found these RES-dependent introns were short, rich in GC and flanked by GC depleted exons, all of which are features associated with intron definition. Using these features, we developed and validated a predictive model that classifies RES dependent introns. Altogether, our study uncovers the essential role of the RES complex during vertebrate development and provides new insights into its function during splicing.


Differences in DNA sequence specificity among MHC class II X box binding proteins.
The class II (Ia) MHC Ag are integral membrane proteins whose expression is limited to specific cell types. A pair of consensus sequences, X and Y, is found upstream from all class II genes and deletion of each of these sequences eliminates expression of transfected genes. Cells that express Ia demonstrate a coordinate response to lymphokines and other stimuli. These conserved sequences might, therefore, play a role in tissue specificity or lymphokine inducibility of Ia gene expression. The X box sequence of the murine class II A alpha gene diverges much more substantially from the X consensus than does the Y box motif of this gene. We demonstrate that this X box motif is nonetheless recognized by sequence-specific DNA-binding proteins, as is the more closely conserved Y box. Gel retardation assays and DNase I footprints were compared for a panel of Ia+ and Ia- cells as well as for cells stimulated with the Ia-inducing lymphokines IL-4 and IFN-gamma. The level, retardation pattern and region of DNA contact were comparable in all instances. Thus the availability of active DNA-binding X and Y box factors cannot alone account for the regulation of A alpha expression. To test whether the same set of proteins binds all class II MHC conserved motifs, oligonucleotide probe binding and cross-competition experiments with X box sequences from A alpha, E alpha, and E beta genes were performed. These studies demonstrated A alpha, E alpha, and E beta DNA-protein complexes with unique mobilities and specificities. In addition, all three X box oligonucleotide probes generated one faint complex with an affinity profile of E beta greater than E alpha much greater than A alpha. These three complexes comigrated and thus may represent a communal binding protein. The data are most consistent with the conclusion that multiple proteins bind class II MHC X boxes. For A alpha, the predominant complexes represent different specificities from the predominant E alpha and E beta X box binding proteins.


Mendelism: New Insights from Gregor Mendel's Lectures in Brno.
Interpretation of Gregor Mendel's work has previously been based on study of his published paper "Experiments in Plant Hybridization." In contrast, the lectures that he gave preceding publication of this work have been largely neglected for more than 150 years. Here, we report on and interpret the content of Mendel's previous two lectures, as they were reported in a local newspaper. We comprehensively reference both the text of his paper and the historical background of his experiments. Our analysis shows that while Mendel had inherited the traditional research program on interspecific hybridization in plants, he introduced the novel method of ratio analysis for representing the variation of unit-characters among offspring of hybrids. His aim was to characterize and explain the developmental features of the distributional pattern of unit-characters in two series of hybrid experiments, using self-crosses and backcrosses with parents. In doing so, he not only answered the question of what the unit-characters were and the nature of their hierarchical classification, but also successfully inferred the numerical principle of unit-character transmission from generation to generation. He also established the nature of the composition and behaviors of reproductive cells from one generation to the next. Here we highlight the evidence from Mendel's lectures, clearly announcing that he had discovered the general law of cross-generation transmission of unit-characters through reproductive cells containing unit-factors. The recovered content of these previous lectures more accurately describes the work he performed with his garden peas than his published paper and shows how he first presented it in Brno. It is thus an invaluable resource for understanding the origin of the science of genetics.


Anatomy adventure: a board game for enhancing understanding of anatomy.
Certain negative factors such as fear, loss of concentration and interest in the course, lack of confidence, and undue stress have been associated with the study of anatomy. These are factors most often provoked by the unusually large curriculum, nature of the course, and the psychosocial impact of dissection. As a palliative measure, Anatomy Adventure, a board game on anatomy was designed to reduce some of these pressures, emphasize student centered and collaborative learning styles, and add fun to the process of learning while promoting understanding and retention of the subject. To assess these objectives, 95 out of over 150 medical and dental students who expressed willingness to be part of the study were recruited and divided into a Game group and a Non-game group. A pretest written examination was given to both groups, participants in the Game group were allowed to play the game for ten days, after which a post-test examination was also given. A 20-item questionnaire rated on a three-point scale to access student's perception of the game was given to the game group. The post-test scores of the game group were significantly higher (P < 0.05) than those of the non-game counterparts. Also the post-test score of the game based group was significantly better (P < 0.05) than their pretest. The students in their feedback noted in very high proportions that the game was interesting, highly informative, encouraged team work, improved their attitude, and perception to gross anatomy.


Endocannabinoids can open the pain gate.
Endocannabinoids produced in the spinal cord can enhance pain by dampening the synapses of inhibitory interneurons that usually prevent the perception of innocuous stimuli as painful. This mechanism promotes pain responsiveness to normally innocuous mechanical stimuli in the skin surrounding a site of injury in both animals and humans subjected to sustained stimulation of pain-sensing nerves. The pain-promoting action of endocannabinoids wanes during the development of chronic pain that is induced by inflammation or nerve injury. This finding may partially explain why, in human trials, cannabinoid drugs have been negative for treatment of most types of acute and postsurgical pain but are effective for some chronic pain states.


Catch rates, composition and fish size from reefs managed with periodically-harvested closures.
Periodically-harvested closures are commonly employed within co-management frameworks to help manage small-scale, multi-species fisheries in the Indo-Pacific. Despite their widespread use, the benefits of periodic harvesting strategies for multi-species fisheries have, to date, been largely untested. We examine catch and effort data from four periodically-harvested reef areas and 55 continuously-fished reefs in Solomon Islands. We test the hypothesis that fishing in periodically-harvested closures would yield: (a) higher catch rates, (b) proportionally more short lived, fast growing, sedentary taxa, and (c) larger finfish and invertebrates, compared to catches from reefs continuously open to fishing. Our study showed that catch rates were significantly higher from periodically-harvested closures for gleaning of invertebrates, but not for line and spear fishing. The family level composition of catches did not vary significantly between open reefs and periodically-harvested closures. Fish captured from periodically-harvested closures were slightly larger, but Trochus niloticus were significantly smaller than those from continuously open reefs. In one case of intense and prolonged harvesting, gleaning catch rates significantly declined, suggesting invertebrate stocks were substantially depleted in the early stages of the open period. Our study suggests periodically-harvested closures can have some short term benefits via increasing harvesting efficiency. However, we did not find evidence that the strategy had substantially benefited multi-species fin-fisheries.


High resolution light intensity spectrum analyzer (LISA) based on Brillouin optical filter.
A high-resolution light intensity spectrum analyzer technique to derive the RF modulation spectrum of optical signals is presented and experimentally confirmed. It uses the XPM nonlinear effect in a dispersion shifted fiber to obtain the light intensity spectrum, and a Brillouin optical filtering method to implement the high resolution spectrometric analysis. Measured RF spectra of PRBS modulated optical signals at 2.5 Gb/s and 10 Gb/s are presented and compared with their corresponding ones obtained in the electrical detection domain to confirm the capabilities of the method.Influence of fiber electrostriction effect is measured and analyzed.


Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns.
Recently, in a randomized, double-blind crossover study, we reported that consumption of grape powder by obese human subjects increased the production of the proinflammatory cytokines interleukin (IL)-1β and IL-6 by peripheral blood monocytes after ex vivo stimulation with bacterial lipopolysaccharide compared with the placebo treatment. We hypothesized that dietary grape powder increased the production of these cytokines by stimulated monocytes. To test this hypothesis, we used 24-hour dietary recall data to determine if differences in dietary patterns played a role in increased cytokine production. No differences in total energy, protein, carbohydrates, or fat intake in the diets were observed between the grape powder and placebo intervention periods. There were no differences observed in consumption of meats and poultry, eggs, fish, vegetables, grains, total dairy, or nuts and seeds by the participants between the 2 intervention periods. When participants received the grape powder, the recall data showed decreased intakes of butyric and capric acids (P<.05), and a possible trend toward decreased intake of cheese and total fruit (P<.1). Positive associations between the intakes of margaric acid, butter, total dairy, or whole grain and IL-6 production were observed (P<.05). However, path analysis showed that total energy, protein, carbohydrates, and fats, and individual fatty acids did not influence the production of cytokines by monocytes. The path analysis indicated that the increased cytokine production by lipopolysaccharide-stimulated monocytes from obese human subjects was caused by the grape powder and not mediated by differences in dietary intake.


Rheological and dynamic insights into an in situ reactive interphase with graft copolymers in multilayered polymer systems.
We provide rheological and dynamic insights into the role of an in situ reactive interphase with graft copolymers in multilayered polymer systems, using a polyamide-6 (PA6)/maleic anhydride grafted poly(vinylidene fluoride) (PVDF-g-MAH) bilayer as a model. Firstly, the influence of the reactive interphase on macroscopic melt flow behavior was studied. The in situ generated interphase from coupling reactions in bilayers significantly contributed to overall viscoelastic responses in both linear and nonlinear regimes. Specifically, under fast extensional flows, the reactively healed bilayer showed enhanced strain hardening mainly due to the formed graft copolymers in the interphase. Secondly, the evolution of a reactive interphase and its effects on microscopic dynamics and structural properties were further probed using dielectric relaxation spectroscopy (DRS). Interestingly, the reactive interphase drastically altered the dielectric responses of the bilayer upon healing, manifesting in the distinct interfacial relaxation/polarization. The relaxation strength of the interfacial polarization increased linearly as a function of reaction time, and was further improved by increasing the number of layers. In agreement with the rheology, DRS also demonstrated the retarded microscopic dynamics of a reactive interphase in healed bilayers. Using the dielectric molecular relaxation spectrum as a probe for the structure, the effects of the reactive interphase on charge dynamics and the resulting structural properties of bilayers were further evaluated. These findings are aimed at providing a better understanding of the effects of the reactive interphase on rheology, dynamics and dielectric properties, towards controlling the interface/interphase in multi micro-/nano-layered polymer structures and for further applications.


Carcass characteristics of cattle differing in Jersey proportion.
Comparison of alternative dairy (cross-)breeding programs requires full appraisals of all revenues and costs, including beef merit. Few studies exist on carcass characteristics of crossbred dairy progeny originating from dairy herds as well as their dams. The objective of the present study was to quantify, using a national database, the carcass characteristics of young animals and cows differing in their fraction of Jersey. The data set consisted of 117,593 young animals and 42,799 cows. The associations between a combination of sire and dam breed proportion (just animal breed proportion when the dependent variable was on cows) with age at slaughter (just for young animals), carcass weight, conformation, fat score, price per kilogram, and total carcass value were estimated using mixed models that accounted for covariances among herdmates of the same sex slaughtered in close proximity in time; we also accounted for age at slaughter in young animals (which was substituted with carcass weight and carcass fat score when the dependent variable was age at slaughter), animal sex, parity of the cow or dam (where relevant), and temporal effects represented by a year-by-month 2-way interaction. For young animals, the heaviest of the dairy carcasses were from the mating of a Holstein-Friesian dam and a Holstein-Friesian sire (323.34 kg), whereas the lightest carcasses were from the mating of a purebred Jersey dam to a purebred Jersey sire which were 46.31 kg lighter (standard error of the difference = 1.21 kg). The young animal carcass weight of an F1 Holstein-Friesian × Jersey cross was 20.4 to 27.0 kg less than that of a purebred Holstein-Friesian animal. The carcass conformation of a Holstein-Friesian young animal was 26% superior to that of a purebred Jersey, translating to a difference of 0.78 conformation units on a scale of 1 to 15. Purebred Holstein-Friesians produced carcasses with less fat than their purebred Jersey counterparts. The difference in carcass price per kilogram among the alternative sire-dam breed combinations investigated was minimal, although large differences existed among the different breed types for overall carcass value; the carcass value of a Holstein-Friesian animal was 20% greater than that of a Jersey animal. Purebred Jersey animals required, on average, 21 d longer to reach a given carcass weight and fat score relative to a purebred Holstein-Friesian. The difference in age at slaughter between a purebred Holstein-Friesian animal and the mating between a Holstein-Friesian sire with a Jersey dam, and vice versa, was between 7.0 and 8.9 d. A 75.8-kg difference in carcass weight existed between the carcass of a purebred Jersey cow and that of a Holstein-Friesian cow; a 50% Holstein-Friesian-50% Jersey cow had a carcass 42.0 kg lighter than that of a purebred Holstein-Friesian cow. Carcass conformation was superior in purebred Holstein-Friesian compared with purebred Jersey cows. Results from this study represent useful input parameters to populate simulation models of alternative breeding programs on dairy farms, and to help beef farmers evaluate the cost-benefit of rearing, for slaughter, animals differing in Jersey fraction.


International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals.
Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, "a common language", for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.


Ajulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast-like cells.
Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, prevents joint tissue injury in rats with adjuvant induced arthritis. Because activation of osteoclasts is central to the pathogenesis of bone erosion in patients with rheumatoid arthritis (RA), we investigated the influence of AjA on osteoclast differentiation and survival. Osteoclast cultures were established by stimulation of RAW264.7 cells and primary mouse bone marrow cultures with receptor activator of NF-kappaB ligand (RANKL). Simultaneous addition of AjA (15 and 30 microM) and RANKL to both culture systems significantly suppressed development of multinucleated osteoclasts (osteoclastogenesis) in a dose dependent manner, as determined by quantification of multinuclear, tartrate-resistant acid phosphatase (TRAP)-positive cells. AjA impaired growth of RAW264.7 monocytes and prevented further osteoclast formation in cultures in which osteoclastogenesis had already begun. Reduction by AjA of both monocyte growth and osteoclast formation was associated with apoptosis, assayed by annexin V and propidium iodide staining, and caspase activity. The anti-osteoclastogenic effects of AjA did not require the continuous presence of AjA in the cell cultures. Based on these findings, we propose that AjA or other nonpsychoactive synthetic analogs of Cannabis constituents may be useful therapy for diseases such as RA and osteoporosis in which bone resorption is a central feature.


Leg orientation as a clinical sign for pusher syndrome.
Effective control of (upright) body posture requires a proper representation of body orientation. Stroke patients with pusher syndrome were shown to suffer from severely disturbed perception of own body orientation. They experience their body as oriented 'upright' when actually tilted by nearly 20 degrees to the ipsilesional side. Thus, it can be expected that postural control mechanisms are impaired accordingly in these patients. Our aim was to investigate pusher patients' spontaneous postural responses of the non-paretic leg and of the head during passive body tilt. A sideways tilting motion was applied to the trunk of the subject in the roll plane. Stroke patients with pusher syndrome were compared to stroke patients not showing pushing behaviour, patients with acute unilateral vestibular loss, and non brain damaged subjects. Compared to all groups without pushing behaviour, the non-paretic leg of the pusher patients showed a constant ipsiversive tilt across the whole tilt range for an amount which was observed in the non-pusher subjects when they were tilted for about 15 degrees into the ipsiversive direction. The observation that patients with acute unilateral vestibular loss showed no alterations of leg posture indicates that disturbed vestibular afferences alone are not responsible for the disordered leg responses seen in pusher patients. Our results may suggest that in pusher patients a representation of body orientation is disturbed that drives both conscious perception of body orientation and spontaneous postural adjustment of the non-paretic leg in the roll plane. The investigation of the pusher patients' leg-to-trunk orientation thus could serve as an additional bedside tool to detect pusher syndrome in acute stroke patients.


BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite.
Intracellular heme is a redox active molecule that can be detrimental to cells at high concentrations or under oxidizing conditions. To prevent accumulation, the inducible enzyme heme oxygenase-1 (HMOX1) catalyzes degradation of heme. In the absence of elevated intracellular heme or oxidative stress, the basic region leucine zipper transcriptional regulator BACH1 binds HMOX1 antioxidant response elements and represses transcription. Conversely, increased intracellular heme or sulfhydryl oxidation inactivate BACH1, permitting transcriptional induction of HMOX1. Here, we investigate the effect of BACH1 inactivation on the induction of HMOX1 and as a mechanism for broader gene induction. We show that BACH1 is inactivated at low micromolar arsenite concentrations and that BACH1 inactivation is necessary and sufficient for transcriptional induction of HMOX1. Because BACH1 is thought to interact with antioxidant response element motifs, we further examined the role of BACH1 as a regulator of inducible antioxidant gene expression by assessing the global profile of gene expression following BACH1 knockdown using small interfering RNA. The loss of BACH1 function in human keratinocytes results almost exclusively in HMOX1 induction, suggesting that BACH1 may function as a rheostat regulating levels of intracellular free heme.


Comparison of different techniques to measure body composition in moderately active adolescents.
To evaluate the differences in the estimate of body fat percentage (%FM) and the amount (kg) of fat free mass (FFM) by different methods in 26 moderately active adolescents very similar in age, body fatness, and training status. Mean (SD) age was 16.7 (0.9) years, height was 177.0 (5.1) cm, and weight 68.0 (5.2) kg. %FM was assessed using dual-energy x ray absorptiometry (DXA) and two skinfold prediction equations: that of Slaughter et al (%FM Sla) and that of Deurenberg et al (%FM Deu). In the same way, FFM was measured using DXA and different impedance equations: those of Suprasongsin et al (FFM Sup), Schaefer et al (FFM Sch), Houtkooper et al (FFM Hou), and Deurenberg et al (FFM Deu). To determine the interchangeability of the different methods of measuring %FM and FFM, one way analysis of variance, standard error (SE), and coefficient of variation (CV%) ((SD/mean) x 100) were used. On average, no significant statistical differences were observed between the values determined for %FM: DXA value, 11.7 (5.4%); %FM Sla, 10.9 (4.0)%; %FM Deu, 11.5 (2.3)%. On the other hand, SE and CV% between each pair of the three methods used showed very large variability. With regard to the measurement or prediction of FFM, the mean value measured by DXA was significantly higher than that predicted by the equation of Sch (+7.2 kg, p < 0.001), Deu (+3.2 kg, p < 0.001), and Hou (+2.6 kg, p < 0.001), whereas it was lower than that predicted by the equation of Sup (-1.6 kg, p < 0.05). The Hou and Deu values were the only two that, on average, did not differ in a statistically significant way, although they showed the highest CV%. In our sample of moderately active adolescents the estimated values for %FM and FFM appear to be highly dependent on method.


The impact of red light cameras on safety in Arizona.
Red light cameras (RLCs) have been used in a number of US cities to yield a demonstrable reduction in red light violations; however, evaluating their impact on safety (crashes) has been relatively more difficult. Accurately estimating the safety impacts of RLCs is challenging for several reasons. First, many safety related factors are uncontrolled and/or confounded during the periods of observation. Second, "spillover" effects caused by drivers reacting to non-RLC equipped intersections and approaches can make the selection of comparison sites difficult. Third, sites selected for RLC installation may not be selected randomly, and as a result may suffer from the regression to the mean bias. Finally, crash severity and resulting costs need to be considered in order to fully understand the safety impacts of RLCs. Recognizing these challenges, a study was conducted to estimate the safety impacts of RLCs on traffic crashes at signalized intersections in the cities of Phoenix and Scottsdale, Arizona. Twenty-four RLC equipped intersections in both cities are examined in detail and conclusions are drawn. Four different evaluation methodologies were employed to cope with the technical challenges described in this paper and to assess the sensitivity of results based on analytical assumptions. The evaluation results indicated that both Phoenix and Scottsdale are operating cost-effective installations of RLCs: however, the variability in RLC effectiveness within jurisdictions is larger in Phoenix. Consistent with findings in other regions, angle and left-turn crashes are reduced in general, while rear-end crashes tend to increase as a result of RLCs.


Use of DNA haplotype analysis in diagnosis of familial hypercholesterolaemia in 31 German families.
In the majority of patients, familial hypercholesterolaemia (FH) is caused by different mutations affecting the well defined low density lipoprotein receptor (LDLR) gene. However, 3% of patients in Munich with a clinical diagnosis of FH have a particular mutation in the apolipoprotein B gene causing familial defective apolipoprotein B-100 (FDB). To date none of the LDLR mutations causing FH in German patients has been identified and it is therefore not yet possible to use DNA technology for direct diagnosis. However, indirect molecular diagnosis based on genetic linkage of common restriction fragment length polymorphisms (RFLPs) of the LDLR gene can be used for diagnosis in family studies. Patients with FDB were excluded from this study. Genotypes and haplotypes of four RFLPs (StuI, ApalI 5', PvuII, and NcoI) were determined in a total of 164 independent alleles from 31 pedigrees that included 222 subjects. Allele frequencies and four RFLP haplotype distribution did not differ significantly from those reported in other populations. The applicability of DNA diagnosis in our lipid clinic is comparable with the estimation from calculations on frequencies and heterozygosities of RFLPs, as predicted using these four RFLPs before. On the basis of cosegregation of haplotypes and normo- or hypercholesterolaemia in one or more sibs or offspring, defective and normal LDLR gene alleles could be distinguished in 42 of 58 heterozygous FH patients who were heterozygous for at least one RFLP. In 97 of 134 (72%) children of these 42 subjects, diagnosis of FH could be carried out unambiguously.(ABSTRACT TRUNCATED AT 250 WORDS)


Energy restriction and oxidative DNA damage in humans.
The cancer-preventive effect of energy restriction in rodents has been related to a decrease in oxidative damage to DNA. We have investigated the effect of energy restriction on the rate of oxidative DNA modification estimated from the urinary excretion of the repair product, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in healthy, normal weight men. Before and after 10 weeks on a diet containing 80 (n = 16) or 100% (n = 8) of the estimated weight-maintaining energy, resting metabolic rate (RMR) was measured and 24-h urine was collected for 8-oxodG determination by HPLC. During the study, the weight loss was 10 and 2.5% of the initial weight, mostly in terms of fat, and the RMR decreased by 13 and 8% in the energy-restricted and control groups, respectively. With the use of t tests there was no significant difference within or between groups with respect to 8-oxodG excretion. However, if RMR was included as a covariate in multifactorial ANOVA, an average relative 17% (2-31%; 95% confidence interval) increase in 8-oxodG excretion in the energy-restricted group was significantly different from the corresponding value of the control group (P < 0.02). In the energy-restricted group the change in 8-oxodG excretion was correlated closely with the decrease in RMR (r = 0.63; P = 0.013). In the present study, 20% energy restriction for 10 weeks did not reduce oxidative DNA damage; we question a beneficial effect on cancer risk in normal weight humans.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.
The absence of 'shovel-ready' anti-coronavirus drugs during vaccine development has exceedingly worsened the SARS-CoV-2 pandemic. Furthermore, new vaccine-resistant variants and coronavirus outbreaks may occur in the near future, and we must be ready to face this possibility. However, efficient antiviral drugs are still lacking to this day, due to our poor understanding of the mode of incorporation and mechanism of action of nucleotides analogs that target the coronavirus polymerase to impair its essential activity. Here, we characterize the impact of remdesivir (RDV, the only FDA-approved anti-coronavirus drug) and other nucleotide analogs (NAs) on RNA synthesis by the coronavirus polymerase using a high-throughput, single-molecule, magnetic-tweezers platform. We reveal that the location of the modification in the ribose or in the base dictates the catalytic pathway(s) used for its incorporation. We show that RDV incorporation does not terminate viral RNA synthesis, but leads the polymerase into backtrack as far as 30 nt, which may appear as termination in traditional ensemble assays. SARS-CoV-2 is able to evade the endogenously synthesized product of the viperin antiviral protein, ddhCTP, though the polymerase incorporates this NA well. This experimental paradigm is essential to the discovery and development of therapeutics targeting viral polymerases.


The Fc gamma RI receptor signals through the activation of hck and MAP kinase.
U937 cells differentiated with IFN-gamma (termed U937IF cells) were used to study Fc gamma RI signaling. IFN induces a functional Fc gamma RI receptor signaling pathway in U937 cells, leading to the activation of the respiratory burst. IFN induces the expression of the nonreceptor protein tyrosine kinase, hck, and cross-linking the Fc gamma RI receptor in U937IF cells results in the activation of hck kinase as evidenced by the three- to fivefold increased tyrosine phosphorylation of hck. In vitro kinase assays demonstrate that the specific kinase activity of hck is increased 10-fold after Fc gamma RI stimulation. hck is observed to associate with two prominent tyrosine-phosphorylated proteins, p72 and p95, after Fc gamma RI-activation. Fc gamma RI cross-linking also results in mobility shift in MAP kinase in U937IF cells, suggesting that the Fc gamma RI receptor signals through the activation of MAP kinase. The data suggest that hck, p72, p95, and MAP kinase are involved in signal transduction through the Fc gamma RI receptor.


Predictive Mathematical Models for the Spread and Treatment of Hyperoxia-induced Photoreceptor Degeneration in Retinitis Pigmentosa.
To determine whether the oxygen toxicity hypothesis can explain the distinctive spatio-temporal patterns of retinal degeneration associated with human retinitis pigmentosa (RP) and to predict the effects of antioxidant and trophic factor treatments under this hypothesis. Three mathematical models were derived to describe the evolution of the retinal oxygen concentration and photoreceptor density over time. The first model considers only hyperoxia-induced degeneration, while the second and third models include mutation-induced rod and cone loss respectively. The models were formulated as systems of partial differential equations, defined on a two-dimensional domain spanning the region between the foveal center and the ora serrata, and were solved numerically using the finite element method. The mathematical models recapitulate patterns of retinal degeneration which involve preferential loss of photoreceptors in the parafoveal/perifoveal and far-peripheral retina, while those which involve a preferential loss of midperipheral photoreceptors cannot be reproduced. Treatment with antioxidants or trophic factors is predicted to delay, halt, or partially reverse retinal degeneration, depending upon the strength and timing of treatment and disease severity. The model simulations indicate that while the oxygen toxicity hypothesis is sufficient to explain some of the patterns of retinal degeneration observed in human RP, additional mechanisms are necessary to explain the full range of behaviors. The models further suggest that antioxidant and trophic factor treatments have the potential to reduce hyperoxia-induced disease severity and that, where possible, these treatments should be targeted at retinal regions with low photoreceptor density to maximize their efficacy.


Regulation of urea and citrulline synthesis under physiological conditions.
Information on the regulation of urea synthesis in vivo was obtained by examining the relationship between ureagenesis in vivo, citrulline synthesis in vitro, and two factors currently hypothesized to exert short-term regulation of this pathway: the liver mitochondrial content of N-acetylglutamate (NAG) and substrate availability. Rats meal-fed for 4 h every day (4-20 schedule) or for 8 h every other day (8-40 schedule) were used. (1) The citrulline-synthesizing capacity of mitochondria from livers of rats on the 8-40 schedule exceeded the corresponding velocity of urea synthesis in vivo at all time points studied. (2) Mitochondrial NAG in these livers increased from 127 +/- 32 pmol/mg of protein at 0 h to 486 +/- 205 pmol/mg at 3 h after the start of a meal, and decreased thereafter, but the correlation between NAG content and the velocity of citrulline synthesis was not simple, suggesting that NAG is not the only determinant of the state of activation of carbamoyl phosphate synthase I. (3) In rats on the 4-20 schedule killed 1 h after the start of the meal, the liver content of ornithine, citrulline, arginine, glutamate, alanine and urea increased 2.1-12-fold with respect to the values at 0 h; glutamine decreased by 39%. (4) The combined findings indicate that in vivo, moment-to-moment control of the velocity of urea synthesis is exerted by substrate availability. (5) Digestion limits the supply of substrate to the liver, and prevents its ureagenic capacity from being overwhelmed following a protein-containing meal.


The use of chitosan-6-mercaptonicotinic acid nanoparticles for oral peptide drug delivery.
The aim of this study was to develop a novel nanoparticulate formulation and test its potential for oral peptide drug delivery. Chitosan-6-mercaptonicotinic acid is a novel thiolated chitosan with strong mucoadhesive properties. Nanoparticles were developed by an ionic gellation method. The obtained particles were characterized in terms of mucoadhesion, stability, toxicity, and in vitro release. Human insulin (HI) was chosen as a model peptide drug, incorporated in the particles and orally administered to rats. Human insulin was quantified in the blood by means of ELISA. The size of the obtained particles was in the range of 200-300 nm and the zeta potential was determined to be +8-+23 depending on the amount of thiol groups attached on the polymer. After 3 h of incubation up to 60% of the thiolated chitosan nanoparticles remained attached to the mucosa in contrast to 20% of unmodified chitosan particles. The AUC of HI after oral administration of thiolated chitosan nanoparticles was 4-fold improved compared to unmodified chitosan nanoparticles. Due to these improvements, chitosan-6-mercaptonicotinic acid nanoparticles are promising vehicles for oral delivery of peptide drugs.


Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies.
Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.


The genome of cowpea (Vigna unguiculata [L.] Walp.).
Cowpea (Vigna unguiculata [L.] Walp.) is a major crop for worldwide food and nutritional security, especially in sub-Saharan Africa, that is resilient to hot and drought-prone environments. An assembly of the single-haplotype inbred genome of cowpea IT97K-499-35 was developed by exploiting the synergies between single-molecule real-time sequencing, optical and genetic mapping, and an assembly reconciliation algorithm. A total of 519 Mb is included in the assembled sequences. Nearly half of the assembled sequence is composed of repetitive elements, which are enriched within recombination-poor pericentromeric regions. A comparative analysis of these elements suggests that genome size differences between Vigna species are mainly attributable to changes in the amount of Gypsy retrotransposons. Conversely, genes are more abundant in more distal, high-recombination regions of the chromosomes; there appears to be more duplication of genes within the NBS-LRR and the SAUR-like auxin superfamilies compared with other warm-season legumes that have been sequenced. A surprising outcome is the identification of an inversion of 4.2 Mb among landraces and cultivars, which includes a gene that has been associated in other plants with interactions with the parasitic weed Striga gesnerioides. The genome sequence facilitated the identification of a putative syntelog for multiple organ gigantism in legumes. A revised numbering system has been adopted for cowpea chromosomes based on synteny with common bean (Phaseolus vulgaris). An estimate of nuclear genome size of 640.6 Mbp based on cytometry is presented.


Analyzing redox balance in a synthetic yeast platform to improve utilization of brown macroalgae as feedstock.
Macroalgae have high potential to be an efficient, and sustainable feedstock for the production of biofuels and other more valuable chemicals. Attempts have been made to enable the co-fermentation of alginate and mannitol by Saccharomyces cerevisiae to unlock the full potential of this marine biomass. However, the efficient use of the sugars derived from macroalgae depends on the equilibrium of cofactors derived from the alginate and mannitol catabolic pathways. There are a number of strong metabolic limitations that have to be tackled before this bioconversion can be carried out efficiently by engineered yeast cells. An analysis of the redox balance during ethanol fermentation from alginate and mannitol by Saccharomyces cerevisiae using metabolic engineering tools was carried out. To represent the strain designed for conversion of macroalgae carbohydrates to ethanol, a context-specific model was derived from the available yeast genome-scale metabolic reconstructions. Flux balance analysis and dynamic simulations were used to determine the flux distributions. The model indicates that ethanol production is determined by the activity of 4-deoxy-l-erythro-5-hexoseulose uronate (DEHU) reductase (DehR) and its preferences for NADH or NADPH which influences strongly the flow of cellular resources. Different scenarios were explored to determine the equilibrium between NAD(H) and NADP(H) that will lead to increased ethanol yields on mannitol and DEHU under anaerobic conditions. When rates of mannitol dehydrogenase and DehRNADH tend to be close to a ratio in the range 1-1.6, high growth rates and ethanol yields were predicted. The analysis shows a number of metabolic limitations that are not easily identified through experimental procedures such as quantifying the impact of the cofactor preference by DEHU reductase in the system, the low flux into the alginate catabolic pathway, and a detailed analysis of the redox balance. These results show that production of ethanol and other chemicals can be optimized if a redox balance is achieved. A possible methodology to achieve this balance is presented. This paper shows how metabolic engineering tools are essential to comprehend and overcome this limitation.


A unified approach to modelling linkage to quantitative and qualitative traits.
For quantitative traits with a genetic component, random effects approaches are used to test for linkage at observed marker loci. We propose to use these approaches also for binary outcomes observed in sib pairs derived from a population-based cohort study. In addition to a random effect modelling correlation due to polygenic effect, a random effect is included to model the correlation between siblings due to sharing alleles identical by descent (IBD) at the observed marker locus. A two-step analysis is proposed. Firstly, score statistics are computed to test whether correlation is present in the data. Secondly, random effects models are fitted, yielding heritability estimates. To illustrate the methods, data on the contribution of the COL2A1 gene to various binary and quantitative outcomes including the presence of Heberden's nodes and bone mineral density (BMD) are analysed. For most of the traits studied, the score statistics were significant, indicating the presence of genetic effects. For BMD and for Heberden's nodes, the variance explained by the marker locus was 44% (P = 0.0008) and 15% (P = 0.38) respectively. We conclude that the score statistics can be used as a preliminary data analysis. In more sophisticated analysis, heritabilities can be estimated by fitting random effects models.


Assessment of a technique for 2D-3D registration of cerebral intra-arterial angiography.
This study assesses the ability of a computer algorithm to perform automated 2D-3D registrations of digitally subtracted cerebral angiograms. The technique was tested on clinical studies of five patients with intracranial aneurysms. The automated procedure was compared against a gold standard manual registration, and achieved a mean registration accuracy of 1.3 mm (SD 0.6 mm). Two registration strategies were tested using coarse (128 x 128 pixel) or fine (256 x 256 pixel) images. The mean registration errors proved similar but registration of the lower resolution images was 3 times quicker (mean registration times 33 s, SD 13 s for low and 150 s SD 48 s for high resolution images). The automated techniques were considerably faster than manual registrations but achieved similar accuracy. The technique has several potential uses but is particularly applicable to endovascular treatment techniques.


Comparison of the effects of zinc deprivation and actinomycin D on ribonucleic acid synthesis by stimulated lymphocytes.
1. EDTA inhibited incorporation of [3H]uridine into RNA of lymphocytes, but did not decrease uptake into the cold-acid-soluble fraction of the cells. The inhibition by EDTA was largely reversible by simultaneous addition of Zn2+. 2. Low concentrations pf actinomycin D (3 ng/ml) added at the time of stimulation of the cells inhibited [3H]uridine incorporation into RNA, but concentrations of 50-100 ng/ml were required to produce the same degree of inhibition if addition of actinomycin D was delayed until just before the incorporation was measured. This difference in sensitivity did not reg within the cells. 3. When added immediately before phytohaemagglutinin, actinomycin D (3 ng/ml) and EDTA produced similar time-courses of inhibition of uridine incorporation. 4. Uridine incorporation at 32h was inhibited when actinomycin D (3 ng/ml) or EDTA was added just before stimulation of the cells, but was only slightly affected when they were added at 32h. At intermediate times the incorporation of uridine remained sensitive to addition of EDTA for longer than it was sensitive to actinomycin D. 5. Polyacrylamide-gel separation of RNA synthesized in EDTA-treated cultures in the presence or absence of added Zn2+ showed that lower availability of Zn2+ resulted in a decreased rate of transfer of radioactivity from 32S to 28S rRNA and decreased survival of 28S rRNA relative to 18S rRNA. 6. Close similarities have been shown to exist between the effects of EDTA and low concentrations of actinomycin D. Not all the effects of EDTA could be explained by postulating that Zn2+ was a constituent of RNA polymerase I, nor were the effects of actinomycin D readily explained by previously suggested mechanisms of action of this antibiotic.


Dental Evidence in Forensic Identification - An Overview, Methodology and Present Status.
Forensic odontology is primarily concerned with the use of teeth and oral structures for identification in a legal context. Various forensic odontology techniques help in the identification of the human remains in incidents such as terrorists' attacks, airplane, train and road accidents, fires, mass murders, and natural disasters such as tsunamis, earth quakes and floods, etc. (Disaster Victim Identification-DVI). Dental structures are the hardest and well protected structures in the body. These structures resist decomposition and high temperatures and are among the last ones to disintegrate after death. The principal basis of the dental identification lies in the fact that no two oral cavities are alike and the teeth are unique to an individual. The dental evidence of the deceased recovered from the scene of crime/occurrence is compared with the ante-mortem records for identification. Dental features such as tooth morphology, variations in shape and size, restorations, pathologies, missing tooth, wear patterns, crowding of the teeth, colour and position of the tooth, rotations and other peculiar dental anomalies give every individual a unique identity. In absence of ante-mortem dental records for comparison, the teeth can help in the determination of age, sex, race/ethnicity, habits, occupations, etc. which can give further clues regarding the identity of the individuals. This piece of writing gives an overview of dental evidence, its use in forensic identification and its limitations.


A domain-based approach for analyzing the function of aluminum-activated malate transporters from wheat (Triticum aestivum) and Arabidopsis thaliana in Xenopus oocytes.
Wheat and Arabidopsis plants respond to aluminum (Al) ions by releasing malate from their root apices via Al-activated malate transporter. Malate anions bind with the toxic Al ions and contribute to the Al tolerance of these species. The genes encoding the transporters in wheat and Arabidopsis, TaALMT1 and AtALMT1, respectively, were expressed in Xenopus laevis oocytes and characterized electrophysiologically using the two-electrode voltage clamp system. The Al-activated currents generated by malate efflux were detected for TaALMT1 but not for AtALMT1. Chimeric proteins were generated by swapping the N- and C-terminal halves of TaALMT1 and AtALMT1 (Ta::At and At::Ta). When these chimeras were characterized in oocytes, Al-activated malate efflux was detected for the Ta::At chimera but not for At::Ta, suggesting that the N-terminal half of TaALMT1 is necessary for function in oocytes. An additional chimera, Ta(48)::At, generated by swapping 17 residues from the N-terminus of AtALMT1 with the equivalent 48 residues from TaALMT1, was sufficient to support transport activity. This 48 residue region includes a helical region with a putative transmembrane domain which is absent in AtALMT1. The deletion of this domain from Ta(48)::At led to the complete loss of transport activity. Furthermore, truncations and a deletion at the C-terminal end of TaALMT1 indicated that a putative helical structure in this region was also required for transport function. This study provides insights into the structure-function relationships of Al-activated ALMT proteins by identifying specific domains on the N- and C-termini of TaALMT1 that are critical for basal transport function and Al responsiveness in oocytes.


Regulating ancillary ligands of Ru(ii) complexes with square-planar quadridentate ligands for more efficient sensitizers in dye-sensitized solar cells: insights from theoretical investigations.
In this work, we designed three dyes (Ru1, Ru2, and Ru3) by modifying the square-planar quadridentate ligand of the experimental Ru(ii) complex K1, [RuL(trans-NCS)2] with L = dimethyl-6,60-bis(methyl-2-pyridylamino)-2,20-bipyridine-4,40-dicarboxylate, from a theoretical viewpoint. As is known, K1 shows obvious advantages over the famous dye N749 in light absorption ability because of its highly conjugated ancillary ligands. Density functional theory and time-dependent density functional theory methods were used to determine the geometrical structures, electronic structures and absorption spectra of the dye complexes. A quantum dynamics method in conjunction with extended Hückel theory was used to simulate the interfacial electron transfer process at the dye-TiO2 interface. The calculated results suggest that Ru1, which contains arylmethane groups, presents improved light absorption and efficient interfacial electron transfer compared with the reference dye K1. We also verified that the position of the anchoring carboxylic acid groups could largely guide the rate of interfacial electron transfer. Ru3, whose anchoring groups are attached to pyridine rings, would have significantly faster interfacial electron transfer than Ru2, whose anchoring groups are attached to the pyrrole ligands; this is because varying the position of the anchoring group results in a difference in the extent of electron donor-acceptor orbital interactions. We expect that the current study will provide some theoretical guidelines for the experimental synthesis of novel Ru(ii) complex dyes.


Complete Genome Sequence of Vitreoscilla sp. Strain C1, Source of the First Bacterial Hemoglobin.
Vitreoscilla sp. strain C1 is of historical importance as the source of the first prokaryotic hemoglobin identified. Vitreoscilla spp. rely on their hemoglobin and cytochrome oxidase to grow in microaerobic environments despite their aerobic nature. To help characterize this historically relevant strain, we sequenced the complete Vitreoscilla sp. strain C1 genome.